Cardiac reperfusion damage prevented by a nitroxide free radical.

Gelvan, Dan; Saltman, Paul; Powell, Saul R.

doi:10.1073/pnas.88.11.4680

Cited by 152 publications

(79 citation statements)

References 27 publications

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“…Another nitroxide, TEMPO, decreased arrhythmia following experimentally induced cardiac ischemia in rats [68]. This beneficial effect was also observed in a study of gerbils in which cerebral ischemia was induced by occluding the common carotid arteries bilaterally [69].…”

Section: Ischemia-reperfusion Injury and Inflammationmentioning

confidence: 52%

The chemistry and biology of nitroxide compounds

Soule

Hyodo

Matsumoto

et al. 2007

Free Radical Biology and Medicine

464

387

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Cyclic nitroxides are a diverse range of stable free radicals that have unique antioxidant properties. Because of their ability to interact with free radicals, they have been used for many years as biophysical tools. During the past 15-20 years, however, many interesting biochemical interactions have been discovered and harnessed for therapeutic applications. Biologically relevant effects of nitroxides have been described including their ability to degrade superoxide and peroxide, inhibit Fenton reactions and undergo radical-radical recombination. Cellular studies defined the activity of nitroxides in vitro. By modifying oxidative stress and altering the redox status of tissues, nitroxides have been found to interact with and alter many metabolic processes. These interactions can be exploited for therapeutic and research use including protection against ionizing radiation, as probes in functional magnetic resonance imaging, cancer prevention and treatment, control of hypertension and weight, and protection from damage resulting from ischemia/reperfusion injury. While much remains to be done, many applications have been well studied and some are presently being tested in clinical trials. The therapeutic and research uses of nitroxide compounds are reviewed here with a focus on the progress from initial development to modern trials.

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Section: Ischemia-reperfusion Injury and Inflammationmentioning

confidence: 52%

The chemistry and biology of nitroxide compounds

Soule

Hyodo

Matsumoto

et al. 2007

Free Radical Biology and Medicine

464

387

View full text Add to dashboard Cite

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“…Note that the residual radicals (about 0.8 mM) were not filtered out of the hyperpolarized solution. TEMPO is however known to have low toxicity 49 and nitroxyl radicals are in fact used as in vivo antioxidants. [50][51][52] …”

Section: Experimental Dissolution Dnpmentioning

confidence: 99%

Feasibility of in vivo15N MRS detection of hyperpolarized 15N labeled choline in rats

Cudalbu

Comment

Kurdzesau

et al. 2010

Phys. Chem. Chem. Phys.

102

125

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The increase of total choline in tumors has become an important biomarker in cancer diagnosis. Choline and choline metabolites can be measured in vivo and in vitro using multinuclear MRS. Recent in vivo 13 C MRS studies using labeled substrates enhanced via dynamic nuclear polarization demonstrated the tremendous potential of hyperpolarization for real-time metabolic studies. The present study demonstrates the feasibility of detecting hyperpolarized 15 N labeled choline in vivo in a rat head at 9.4 T. We furthermore report the in vitro (172 AE 16 s) and in vivo (126 AE 15 s) longitudinal relaxation times. We conclude that with appropriate infusion protocols it is feasible to detect hyperpolarized 15 N labeled choline in live animals.

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“…TEMPO is employed extensively in cell and animal models; it has the advantages of being water-soluble, low-molecular weight, membrane-permeable, and commercially available. Studies have demonstrated the protective properties of TEMPO in various pathological situations, including radiation injury (Cuscela et al, 1996) and ischemia/reperfusion injury (Gelvan et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Nitroxide TEMPO: A genotoxic and oxidative stress inducer in cultured cells

Guo

Mittelstaedt

Guo

et al. 2013

Toxicology in Vitro

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Abstract2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) is a low molecular weight nitroxide and stable free radical. In this study, we investigated the cytotoxicity and genotoxicity of TEMPO in mammalian cells using the mouse lymphoma assay (MLA) and in vitro micronucleus assay. In the absence of metabolic activation (S9), 3 mM TEMPO produced significant cytotoxicity and marginal mutagenicity in the MLA; in the presence of S9, treatment of mouse lymphoma cells with 1-2 mM TEMPO resulted in dose-dependent decreases of the relative total growth and increases in mutant frequency. Treatment of TK6 human lymphoblastoid cells with 0.9-2.3 mM TEMPO increased the frequency of both micronuclei (a marker for clastogenicity) and hypodiploid nuclei (a marker of aneugenicity) in a dose-dependent manner; greater responses were produced in the presence of S9. Within the dose range tested, TEMPO induced reactive oxygen species and decreased glutathione levels in mouse lymphoma cells. In addition, the majority of TEMPO-induced mutants had loss of heterozygosity at the Tk locus, with allele loss of ≤34 Mbp.These results indicate that TEMPO is mutagenic in the MLA and induces micronuclei and hypodiploid nuclei in TK6 cells. Oxidative stress may account for part of the genotoxicity induced by TEMPO in both cell lines.

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Cardiac reperfusion damage prevented by a nitroxide free radical.

Cited by 152 publications

References 27 publications

The chemistry and biology of nitroxide compounds

The chemistry and biology of nitroxide compounds

Feasibility of in vivo15N MRS detection of hyperpolarized 15N labeled choline in rats

Nitroxide TEMPO: A genotoxic and oxidative stress inducer in cultured cells

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